Immunomodulatory Il-2 Agents in Combination With Immune Checkpoint Inhibitors

Abstract

The invention provides compositions and methods of treating cancer in a patient with a combination therapy comprising a fusion protein of SEQ ID NO: 1 in combination with an immune checkpoint inhibitor. Preferably the patient has failed to achieve complete or partial response with prior or ongoing treatment with an immune checkpoint inhibitor.

1 . A method of treating platinum-resistant ovarian cancer in a patient in need thereof, the method comprising:
 i) administering to the patient a therapeutically effective amount of the fusion protein of SEQ ID NO: 1, or a variant thereof; and   ii) administering to the patient a therapeutically effective amount of an immune checkpoint inhibitor;   wherein step (i) is carried out before, after or simultaneously with step (ii),   wherein the patient has previously failed to achieve complete or partial response to prior treatment or to ongoing treatment with an immune checkpoint inhibitor, and   wherein the variant fusion protein is at least 80% identical to full length SEQ ID NO: 1.   
     
     
         2 . The method of  claim 1 , wherein the patient has previously failed to achieve complete or partial response to prior treatment or to ongoing treatment with an immune checkpoint inhibitor as determined by RECIST (Response Evaluation Criteria In Solid Tumors) criteria or according to the irRECIST (immune-related Response Evaluation Criteria In Solid Tumors) criteria. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the immune checkpoint inhibitor is an anti-PD-1 antibody or an anti PD-L1 antibody. 
     
     
         5 . The method of  claim 1 , wherein the immune checkpoint inhibitor is pembrolizumab. 
     
     
         6 . The method of  claim 1 , wherein the immune checkpoint inhibitor is an anti-CTLA4 antibody. 
     
     
         7 . The method of  claim 1 , wherein the immune checkpoint inhibitor is ipilimumab. 
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the fusion protein of SEQ ID NO: 1 or variant thereof is administered intravenously to the patient. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein a therapeutically effective amount of the fusion protein of SEQ ID NO: 1 or variant thereof is a dose of the fusion protein of SEQ ID NO: 1 or variant thereof of about 0.1 μg/kg, 0.3 μg/kg, 1 μg/kg, 3 μg/kg, 3.5 μg/kg, 4 μg/kg, 4.5 μg/kg, 5 μg/kg, 5.5 μg/kg, 6 μg/kg, 6.5 μg/kg, 7 μg/kg, 7.5 μg/kg, 8 μg/kg, 8.5 μg/kg, 9 μg/kg, 9.5 μg/kg, 10 μg/kg, 10.5 μg/kg, 11 μg/kg, 11.5 μg/kg, 12 μg/kg, 12.5 μg/kg, 13 μg/kg, 13.5 μg/kg, 14 μg/kg, or 14.5 μg/kg. 
     
     
         12 . The method of  claim 11 , wherein the fusion protein of SEQ ID NO: 1 or variant thereof is administered to the patient at a dose of about 6 μg/kg. 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the fusion protein of SEQ ID NO: 1 or variant thereof is administered to the patient daily for five consecutive days. 
     
     
         15 .- 17 . (canceled) 
     
     
         18 . The method of  claim 5 , wherein the pembrolizumab is administered to the patient at a dose of 200 mg. 
     
     
         19 . The method of  claim 18 , wherein pembrolizumab is administered intravenously to the patient. 
     
     
         20 . The method of  claim 19 , wherein pembrolizumab is administered to the patient once every three weeks. 
     
     
         21 . The method of  claim 5 , wherein:
 the fusion protein of SEQ ID NO: 1 or variant thereof is administered intravenously to the patient at a dose of about 6-3 μg/kg daily for five consecutive days, every three weeks, and   wherein the pembrolizumab is administered intravenously to the patient at a dose of about 200 mg once every three weeks.   
     
     
         22 .- 28 . (canceled) 
     
     
         29 . The method of  claim 1 , wherein the patient failed to achieve complete remission (CR) following prior immune checkpoint inhibitor therapy. 
     
     
         30 . The method of  claim 1 , wherein the patient has stable disease (SD), or partial response (PR) with no further reduction in tumor size or response, following prior immune checkpoint inhibitor therapy. 
     
     
         31 . The method of  claim 29 , wherein the prior immune checkpoint inhibitor therapy comprises one or more of anti-PD-1 therapy, anti-PD-L1 therapy, and anti-CTLA-4 therapy. 
     
     
         32 .- 34 . (canceled) 
     
     
         35 . The method of  claim 1 , wherein the fusion protein consists of SEQ ID NO: 1. 
     
     
         36 . The method of  claim 21 , wherein the fusion protein consists of SEQ ID NO: 1.